Higher circulating sphingosine 1-phosphate levels are associated with lower bone mineral density and higher bone resorption marker in humans.

CONTEXT: Several in vivo and in vitro studies suggest that sphingosine-1-phosphate (S1P) is known to act as a coupling factor, to stimulate osteoclastogenesis, to control the migration of osteoclast precursors between the blood and bone, and to stimulate the proliferation, migration, and survival of osteoblasts. OBJECTIVE: Using the determination of circulating S1P levels, we investigated which kinds of processes may be primarily affected by S1P in humans. DESIGN AND SETTING: This was a cross-sectional study conducted in two clinical units in Korea. PARTICIPANTS: Men (n = 86), premenopausal women (n = 94), and postmenopausal women (n = 357) participated in the study. MAIN OUTCOME MEASURES: We measured S1P levels and their relationships with bone mineral density, biochemical bone turnover markers, and uncoupling indices. RESULTS: S1P levels were significantly higher in the postmenopausal women than in the premenopausal women and men. High S1P concentrations were significantly associated with low bone mineral density values at some femur sites in the postmenopausal women (P = 0.015 to 0.049), at the lumbar spine in the premenopausal women (P = 0.017), and at all sites in men (P = 0.001 to 0.036) after adjustments with multiple covariates. S1P levels were positively correlated with bone resorption markers (P = 0.003 to 0.049), but not with formation markers in postmenopausal women. Higher S1P levels were associated with lower uncoupling indices (P = <0.001 to 0.048) in postmenopausal women. CONCLUSION: These findings suggest that S1P may primarily affect bone resorption, resulting in bone loss.